We are using our understanding of heart muscle biology to discover new medicines targeted at disruptions in heart muscle contraction.

Preclinical

Phase 1

Phase 2

Phase 3

hypertrophic cardiomyopathy

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Mavacamten

open

Obstructive HCM

Non-obstructive HCM

close

Mavacamten

for Obstructive & Non-obstructive Hypertrophic Cardiomyopathy

Mavacamten is a first-in-class small molecule therapeutic that reversibly binds to myosin to directly target the excess contractility and impaired relaxation underlying hypertrophic cardiomyopathy, or HCM. MyoKardia has advanced mavacamten into multiple late-stage clinical studies looking at its potential to treat the obstructive and non-obstructive forms of HCM. Our pivotal Phase 3 EXPLORER-HCM clinical trial of mavacamten is designed to demonstrate improvements in symptoms and function in patients with symptomatic obstructive HCM. We expect to report data from the EXPLORER-HCM clinical trial in the second quarter of 2020.

Mavacamten is also being studied in a Phase 2 clinical trial, known as MAVERICK-HCM, in symptomatic non-obstructive HCM patients. The MAVERICK-HCM trial is primarily a dose-ranging study to assess safety and tolerability in the non-obstructive HCM population. Topline data from the Phase 2 MAVERICK-HCM clinical trial is anticipated in the fourth quarter of 2019.

Both the EXPLORER-HCM and MAVERICK-HCM clinical trials were guided and informed by MyoKardia’s Phase 2 PIONEER-HCM trial of mavacamten in patients with symptomatic, obstructive HCM. In the open-label Phase 2 PIONEER-HCM dose-ranging study, treatment with mavacamten for twelve weeks resulted in significant improvements across the primary and secondary endpoints measured. Among the most noteworthy findings were that mavacamten could be dosed to reduce left ventricular outflow tract (LVOT) gradient below the guideline-based definition for obstruction. Along with LVOT gradient reductions, patients experienced improvements in New York Heart Association (NYHA) functional classification and exercise capacity as measured by peak VO2 levels. Reductions in shortness of breath and in levels of NT-proBNP, a well-established marker of ventricular wall stress, were also observed.

Importantly, mavacamten has been well tolerated. We are conducting two long-term extension studies to evaluate safety and activity with chronic dosing of mavacamten. The PIONEER open-label extension (PIONEER-OLE) enrolled patients who participated in MyoKardia’s Phase 2 PIONEER-HCM clinical trial. Twelve- and twenty-four-week data from PIONEER-OLE show that mavacamten could be dosed on an individualized basis to eliminate LVOT gradient while maintaining ejection fractions above the normal range. The MAVA long-term extension (MAVA-LTE) study is enrolling participants from the MAVERICK-HCM and EXPLORER-HCM clinical trials.

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MYK-224

open

HCM

close

MYK-224

MYK-224 is our second therapeutic candidate that specifically targets cardiac myosin to reduce the excess myosin-actin cross-bridge formation underlying HCM. MYK-224 is designed to preserve the unique advantages of mavacamten’s mechanism, including the ability to reduce excess contractility and potentially address impaired relaxation while reducing pharmacokinetic variability. With a shorter half life, MYK-224 may reduce the time required to achieve steady state and thereby provide dosing flexibility. We initiated a Phase 1 clinical study of MYK-224 in healthy volunteers in August 2019 with initial data anticpated in mid-2020.

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LUS-1

open

Precision Diastolic Disease Indications

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LUS-1

Our LUS-1 discovery-stage program is identifying novel therapeutics that target diastolic relaxation without reducing the force of contraction. In preclinical studies of LUS-1 molecules, we have observed improved compliance without a loss of stroke volume.

MYK-491 is an orally-administered small molecule designed to increase the number of myosin-actin cross-bridges formed during cardiac muscle contraction while having minimal impact on diastolic function. The goal is to increase the ensemble force of contraction and improve cardiac output during systole without detracting from the ability of the heart to relax and fill with blood during diastole. MYK-491 is currently in a Phase 1/b2a multiple-ascending dose clinical trial. Up to 40 DCM patients with stable heart failure will be randomized to receive either MYK-491 or placebo for one week, during which time patients will be monitored to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MYK-491. We anticipate reporting data from the Phase 2a study in the fourth quarter of 2019.

Our Phase 1 clinical development program for MYK-491 principally evaluated the safety and tolerability of MYK-491 in healthy human subjects and dilated cardiomyopathy patients. In DCM patients with stable heart failure, administration of MYK-491 resulted in approximately 10 percent relative increases from baseline in cardiac contractility across multiple echocardiographic measures, including stroke volume, left ventricular ejection fraction and fractional shortening. In increasing the heart’s contractility, MYK-491 did not appear to meaningfully change duration of the contraction or the heart’s ability to relax and fill with oxygenated blood. Overall, these data were consistent with results previously reported from the single-ascending dose trial of MYK-491 in healthy volunteers.

MYK-491 was generally well tolerated across the range of oral doses tested in our first-in-human, Phase 1 clinical trial in healthy volunteers. Adverse events observed were benign and transient. Results from our Phase 1a and Phase 1b studies served to inform the starting dose for the Phase 2a study.

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ACT-1

open

Precision Systolic Disease Indications

close

ACT-1

ACT-1 is our preclinical activator program targeting DCM due to sarcomeric mutations and impaired calcium regulation. In preclinical models, our ACT-1 prototype molecules successfully increase contractility, without prolonging systolic ejection time and with minimal impact on relaxation. We currently anticipate advancing our first ACT-1 program compound into clinical development in late 2020 or early 2021.

Mavacamten is a first-in-class small molecule therapeutic that reversibly binds to myosin to directly target the excess contractility and impaired relaxation underlying hypertrophic cardiomyopathy, or HCM. MyoKardia has advanced mavacamten into multiple late-stage clinical studies looking at its potential to treat the obstructive and non-obstructive forms of HCM. Our pivotal Phase 3 EXPLORER-HCM clinical trial of mavacamten is designed to demonstrate improvements in symptoms and function in patients with symptomatic obstructive HCM. We expect to report data from the EXPLORER-HCM clinical trial in the second quarter of 2020.

Mavacamten is also being studied in a Phase 2 clinical trial, known as MAVERICK-HCM, in symptomatic non-obstructive HCM patients. The MAVERICK-HCM trial is primarily a dose-ranging study to assess safety and tolerability in the non-obstructive HCM population. Topline data from the Phase 2 MAVERICK-HCM clinical trial is anticipated in the fourth quarter of 2019.

Both the EXPLORER-HCM and MAVERICK-HCM clinical trials were guided and informed by MyoKardia’s Phase 2 PIONEER-HCM trial of mavacamten in patients with symptomatic, obstructive HCM. In the open-label Phase 2 PIONEER-HCM dose-ranging study, treatment with mavacamten for twelve weeks resulted in significant improvements across the primary and secondary endpoints measured. Among the most noteworthy findings were that mavacamten could be dosed to reduce left ventricular outflow tract (LVOT) gradient below the guideline-based definition for obstruction. Along with LVOT gradient reductions, patients experienced improvements in New York Heart Association (NYHA) functional classification and exercise capacity as measured by peak VO2 levels. Reductions in shortness of breath and in levels of NT-proBNP, a well-established marker of ventricular wall stress, were also observed.

Importantly, mavacamten has been well tolerated. We are conducting two long-term extension studies to evaluate safety and activity with chronic dosing of mavacamten. The PIONEER open-label extension (PIONEER-OLE) enrolled patients who participated in MyoKardia’s Phase 2 PIONEER-HCM clinical trial. Twelve- and twenty-four-week data from PIONEER-OLE show that mavacamten could be dosed on an individualized basis to eliminate LVOT gradient while maintaining ejection fractions above the normal range. The MAVA long-term extension (MAVA-LTE) study is enrolling participants from the MAVERICK-HCM and EXPLORER-HCM clinical trials.

MYK-224 is our second therapeutic candidate that specifically targets cardiac myosin to reduce the excess myosin-actin cross-bridge formation underlying HCM. MYK-224 is designed to preserve the unique advantages of mavacamten’s mechanism, including the ability to reduce excess contractility and potentially address impaired relaxation while reducing pharmacokinetic variability. With a shorter half life, MYK-224 may reduce the time required to achieve steady state and thereby provide dosing flexibility. We initiated a Phase 1 clinical study of MYK-224 in healthy volunteers in August 2019 with initial data anticpated in mid-2020.

Our LUS-1 discovery-stage program is identifying novel therapeutics that target diastolic relaxation without reducing the force of contraction. In preclinical studies of LUS-1 molecules, we have observed improved compliance without a loss of stroke volume.

MYK-491 is an orally-administered small molecule designed to increase the number of myosin-actin cross-bridges formed during cardiac muscle contraction while having minimal impact on diastolic function. The goal is to increase the ensemble force of contraction and improve cardiac output during systole without detracting from the ability of the heart to relax and fill with blood during diastole. MYK-491 is currently in a Phase 1/b2a multiple-ascending dose clinical trial. Up to 40 DCM patients with stable heart failure will be randomized to receive either MYK-491 or placebo for one week, during which time patients will be monitored to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MYK-491. We anticipate reporting data from the Phase 2a study in the fourth quarter of 2019.

Our Phase 1 clinical development program for MYK-491 principally evaluated the safety and tolerability of MYK-491 in healthy human subjects and dilated cardiomyopathy patients. In DCM patients with stable heart failure, administration of MYK-491 resulted in approximately 10 percent relative increases from baseline in cardiac contractility across multiple echocardiographic measures, including stroke volume, left ventricular ejection fraction and fractional shortening. In increasing the heart’s contractility, MYK-491 did not appear to meaningfully change duration of the contraction or the heart’s ability to relax and fill with oxygenated blood. Overall, these data were consistent with results previously reported from the single-ascending dose trial of MYK-491 in healthy volunteers.

MYK-491 was generally well tolerated across the range of oral doses tested in our first-in-human, Phase 1 clinical trial in healthy volunteers. Adverse events observed were benign and transient. Results from our Phase 1a and Phase 1b studies served to inform the starting dose for the Phase 2a study.

ACT-1 is our preclinical activator program targeting DCM due to sarcomeric mutations and impaired calcium regulation. In preclinical models, our ACT-1 prototype molecules successfully increase contractility, without prolonging systolic ejection time and with minimal impact on relaxation. We currently anticipate advancing our first ACT-1 program compound into clinical development in late 2020 or early 2021.

Mavacamten is a first-in-class small molecule therapeutic that reversibly binds to myosin to directly target the excess contractility and impaired relaxation underlying hypertrophic cardiomyopathy, or HCM. MyoKardia has advanced mavacamten into multiple late-stage clinical studies looking at its potential to treat the obstructive and non-obstructive forms of HCM. Our pivotal Phase 3 EXPLORER-HCM clinical trial of mavacamten is designed to demonstrate improvements in symptoms and function in patients with symptomatic obstructive HCM. We expect to report data from the EXPLORER-HCM clinical trial in the second quarter of 2020.

Mavacamten is also being studied in a Phase 2 clinical trial, known as MAVERICK-HCM, in symptomatic non-obstructive HCM patients. The MAVERICK-HCM trial is primarily a dose-ranging study to assess safety and tolerability in the non-obstructive HCM population. Topline data from the Phase 2 MAVERICK-HCM clinical trial is anticipated in the fourth quarter of 2019.

Both the EXPLORER-HCM and MAVERICK-HCM clinical trials were guided and informed by MyoKardia’s Phase 2 PIONEER-HCM trial of mavacamten in patients with symptomatic, obstructive HCM. In the open-label Phase 2 PIONEER-HCM dose-ranging study, treatment with mavacamten for twelve weeks resulted in significant improvements across the primary and secondary endpoints measured. Among the most noteworthy findings were that mavacamten could be dosed to reduce left ventricular outflow tract (LVOT) gradient below the guideline-based definition for obstruction. Along with LVOT gradient reductions, patients experienced improvements in New York Heart Association (NYHA) functional classification and exercise capacity as measured by peak VO2 levels. Reductions in shortness of breath and in levels of NT-proBNP, a well-established marker of ventricular wall stress, were also observed.

Importantly, mavacamten has been well tolerated. We are conducting two long-term extension studies to evaluate safety and activity with chronic dosing of mavacamten. The PIONEER open-label extension (PIONEER-OLE) enrolled patients who participated in MyoKardia’s Phase 2 PIONEER-HCM clinical trial. Twelve- and twenty-four-week data from PIONEER-OLE show that mavacamten could be dosed on an individualized basis to eliminate LVOT gradient while maintaining ejection fractions above the normal range. The MAVA long-term extension (MAVA-LTE) study is enrolling participants from the MAVERICK-HCM and EXPLORER-HCM clinical trials.

MYK-224 is our second therapeutic candidate that specifically targets cardiac myosin to reduce the excess myosin-actin cross-bridge formation underlying HCM. MYK-224 is designed to preserve the unique advantages of mavacamten’s mechanism, including the ability to reduce excess contractility and potentially address impaired relaxation while reducing pharmacokinetic variability. With a shorter half life, MYK-224 may reduce the time required to achieve steady state and thereby provide dosing flexibility. We initiated a Phase 1 clinical study of MYK-224 in healthy volunteers in August 2019 with initial data anticpated in mid-2020.

Our LUS-1 discovery-stage program is identifying novel therapeutics that target diastolic relaxation without reducing the force of contraction. In preclinical studies of LUS-1 molecules, we have observed improved compliance without a loss of stroke volume.

MYK-491 is an orally-administered small molecule designed to increase the number of myosin-actin cross-bridges formed during cardiac muscle contraction while having minimal impact on diastolic function. The goal is to increase the ensemble force of contraction and improve cardiac output during systole without detracting from the ability of the heart to relax and fill with blood during diastole. MYK-491 is currently in a Phase 1/b2a multiple-ascending dose clinical trial. Up to 40 DCM patients with stable heart failure will be randomized to receive either MYK-491 or placebo for one week, during which time patients will be monitored to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MYK-491. We anticipate reporting data from the Phase 2a study in the fourth quarter of 2019.

Our Phase 1 clinical development program for MYK-491 principally evaluated the safety and tolerability of MYK-491 in healthy human subjects and dilated cardiomyopathy patients. In DCM patients with stable heart failure, administration of MYK-491 resulted in approximately 10 percent relative increases from baseline in cardiac contractility across multiple echocardiographic measures, including stroke volume, left ventricular ejection fraction and fractional shortening. In increasing the heart’s contractility, MYK-491 did not appear to meaningfully change duration of the contraction or the heart’s ability to relax and fill with oxygenated blood. Overall, these data were consistent with results previously reported from the single-ascending dose trial of MYK-491 in healthy volunteers.

MYK-491 was generally well tolerated across the range of oral doses tested in our first-in-human, Phase 1 clinical trial in healthy volunteers. Adverse events observed were benign and transient. Results from our Phase 1a and Phase 1b studies served to inform the starting dose for the Phase 2a study.

ACT-1 is our preclinical activator program targeting DCM due to sarcomeric mutations and impaired calcium regulation. In preclinical models, our ACT-1 prototype molecules successfully increase contractility, without prolonging systolic ejection time and with minimal impact on relaxation. We currently anticipate advancing our first ACT-1 program compound into clinical development in late 2020 or early 2021.

ACT-1 is our preclinical activator program targeting DCM due to sarcomeric mutations and impaired calcium regulation. In preclinical models, our ACT-1 prototype molecules successfully increase contractility, without prolonging systolic ejection time and with minimal impact on relaxation. We currently anticipate advancing our first ACT-1 program compound into clinical development in late 2020 or early 2021.

Coming together as a community.

For me, the SHaRe registry demonstrates what we can do when we come together as a community with a shared goal and a spirit of collaboration. The collective data from leading centers is producing a greater understanding of the burden of HCM on patients’ lives. And in turn, SHaRe has grown into a resource for patients to learn about the latest research and to gather for education and support.